LDS5
MCID: LYS020
MIFTS: 26

Loeys-Dietz Syndrome 5 (LDS5)

Categories: Bone diseases, Cardiovascular diseases, Eye diseases, Fetal diseases, Genetic diseases, Immune diseases, Rare diseases

Aliases & Classifications for Loeys-Dietz Syndrome 5

MalaCards integrated aliases for Loeys-Dietz Syndrome 5:

Name: Loeys-Dietz Syndrome 5 57 12 75 29 6
Rienhoff Syndrome 57 53 75 37 73
Lds5 57 12 75
Rnhf 57 12 75
Syndrome, Loeys-Dietz, Type 5 ) 40
Rienhoff Syndrome; Rnhf 57
Reinhoff Syndrome 12

Characteristics:

OMIM:

57
Inheritance:
autosomal dominant

Miscellaneous:
autoimmune manifestations are present in some patients


HPO:

32
loeys-dietz syndrome 5:
Inheritance autosomal dominant inheritance


Classifications:



Summaries for Loeys-Dietz Syndrome 5

OMIM : 57 Loeys-Dietz syndrome-5 (LDS5), also known as Rienhoff (pronounced REENhoff) syndrome, is characterized by syndromic presentation of aortic aneurysms involving the thoracic and/or abdominal aorta, with risk of dissection and rupture. Other systemic features include cleft palate, bifid uvula, mitral valve disease, skeletal overgrowth, cervical spine instability, and clubfoot deformity; however, not all clinical features occur in all patients. In contrast to other forms of LDS (see 609192), no striking aortic or arterial tortuosity is present in these patients, and there is no strong evidence for early aortic dissection (summary by Bertoli-Avella et al., 2015). For a general phenotypic description and a discussion of genetic heterogeneity of Loeys-Dietz syndrome, see LDS1 (609192). (615582)

MalaCards based summary : Loeys-Dietz Syndrome 5, is also known as rienhoff syndrome. An important gene associated with Loeys-Dietz Syndrome 5 is TGFB3 (Transforming Growth Factor Beta 3), and among its related pathways/superpathways are MAPK signaling pathway and FoxO signaling pathway. Affiliated tissues include skin, eye and bone, and related phenotypes are hypertelorism and pectus excavatum

Disease Ontology : 12 A Loeys-Dietz syndrome that has material basis in heterozygous mutation in the TGFB3 gene on chromosome 14q24.

UniProtKB/Swiss-Prot : 75 Loeys-Dietz syndrome 5: A form of Loeys-Dietz syndrome, a syndrome with widespread systemic involvement characterized by arterial tortuosity and aneurysms, hypertelorism, and bifid uvula or cleft palate. LDS5 additional variable features include mitral valve disease, skeletal overgrowth, cervical spine instability, and clubfoot deformity. LDS5 patients do not manifest remarkable aortic or arterial tortuosity, and there is no strong evidence for early aortic dissection.

Related Diseases for Loeys-Dietz Syndrome 5

Symptoms & Phenotypes for Loeys-Dietz Syndrome 5

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Eyes:
hypertelorism
exotropia
ptosis (rare)
downslanting palpebral fissures (in some patients)
blue sclerae (in some patients)
more
Abdomen External Features:
inguinal hernia

Head And Neck Mouth:
cleft palate
bifid uvula
high-arched palate

Skeletal Limbs:
joint hypermobility
increased arm span

Skeletal Spine:
kyphoscoliosis
spondylolisthesis (rare)
cervical spine instability (rare)

Cardiovascular Heart:
atrial septal defect (rare)
ventricular septal defect (rare)
mitral insufficiency
aortic insufficiency, mild (rare)
patent foramen ovale (rare)
more
Cardiovascular Vascular:
aortic root dilation
aneurysm of abdominal aorta
varices
aneurysm of thoracic aorta
aneurysmal dissection or rupture
more
Head And Neck Head:
dolichocephaly (in some patients)
brachycephaly (rare)
metopic ridge, small (rare)

Skin Nails Hair Skin:
easy bruising (in some patients)
thin translucent skin (in some patients)
soft velvety skin (in some patients)

Growth Other:
growth retardation (rare)

Skeletal:
osteoarthritis, early onset (in some patients)

Muscle Soft Tissue:
subcutaneous fat markedly reduced (in some patients)
decreased muscle mass (in some patients)

Chest External Features:
pectus excavatum
pectus carinatum

Skeletal Feet:
pes planus
clubfeet (in some patients)
camptodactyly of toes (in some patients)
pes adductus, transient postnatal (rare)

Skeletal Hands:
arachnodactyly
bilateral contractures of fingers (rare)
palmar flexion, transient postnatal (rare)

Growth Height:
tall stature
short stature (rare)

Chest Diaphragm:
hiatal hernia

Head And Neck Face:
retrognathia, mild
long face (in some patients)
smooth philtrum (rare)
wide face (rare)
midface hypoplasia (rare)

Neurologic Central Nervous System:
delayed motor development (in some patients)
congenital hypotonia, mild (in some patients)
cerebral hemorrhage (rare)

Skeletal Skull:
dolichocephaly (in some patients)
brachycephaly (rare)
metopic ridge, small (rare)

Growth Weight:
low birth weight (in some patients)

Chest Ribs Sternum Clavicles And Scapulae:
scapulae alata (rare)

Skeletal Pelvis:
bilateral coxa valga (rare)


Clinical features from OMIM:

615582

Human phenotypes related to Loeys-Dietz Syndrome 5:

32 (show all 44)
# Description HPO Frequency HPO Source Accession
1 hypertelorism 32 very rare (1%) HP:0000316
2 pectus excavatum 32 very rare (1%) HP:0000767
3 osteoarthritis 32 occasional (7.5%) HP:0002758
4 high palate 32 HP:0000218
5 ptosis 32 occasional (7.5%) HP:0000508
6 inguinal hernia 32 HP:0000023
7 pectus carinatum 32 HP:0000768
8 pes planus 32 very rare (1%) HP:0001763
9 smooth philtrum 32 occasional (7.5%) HP:0000319
10 neonatal hypotonia 32 HP:0001319
11 short stature 32 HP:0004322
12 decreased muscle mass 32 HP:0003199
13 brachycephaly 32 occasional (7.5%) HP:0000248
14 cleft palate 32 very rare (1%) HP:0000175
15 retrognathia 32 HP:0000278
16 dolichocephaly 32 occasional (7.5%) HP:0000268
17 motor delay 32 occasional (7.5%) HP:0001270
18 talipes equinovarus 32 occasional (7.5%) HP:0001762
19 mitral regurgitation 32 HP:0001653
20 arachnodactyly 32 very rare (1%) HP:0001166
21 joint hypermobility 32 HP:0001382
22 downslanted palpebral fissures 32 occasional (7.5%) HP:0000494
23 spondylolisthesis 32 occasional (7.5%) HP:0003302
24 ascending aortic dissection 32 very rare (1%) HP:0004933
25 long face 32 occasional (7.5%) HP:0000276
26 ventricular septal defect 32 occasional (7.5%) HP:0001629
27 bruising susceptibility 32 occasional (7.5%) HP:0000978
28 midface retrusion 32 occasional (7.5%) HP:0011800
29 hyporeflexia 32 HP:0001265
30 proptosis 32 HP:0000520
31 blue sclerae 32 HP:0000592
32 cerebral hemorrhage 32 occasional (7.5%) HP:0001342
33 hiatus hernia 32 HP:0002036
34 tall stature 32 very rare (1%) HP:0000098
35 bifid uvula 32 very rare (1%) HP:0000193
36 kyphoscoliosis 32 very rare (1%) HP:0002751
37 aortic regurgitation 32 occasional (7.5%) HP:0001659
38 small for gestational age 32 HP:0001518
39 exotropia 32 HP:0000577
40 patent foramen ovale 32 occasional (7.5%) HP:0001655
41 bilateral coxa valga 32 HP:0010665
42 increased arm span 32 HP:0012771
43 broad face 32 occasional (7.5%) HP:0000283
44 cervical spine instability 32 occasional (7.5%) HP:0010646

Drugs & Therapeutics for Loeys-Dietz Syndrome 5

Search Clinical Trials , NIH Clinical Center for Loeys-Dietz Syndrome 5

Genetic Tests for Loeys-Dietz Syndrome 5

Genetic tests related to Loeys-Dietz Syndrome 5:

# Genetic test Affiliating Genes
1 Loeys-Dietz Syndrome 5 29 TGFB3

Anatomical Context for Loeys-Dietz Syndrome 5

MalaCards organs/tissues related to Loeys-Dietz Syndrome 5:

41
Skin, Eye, Bone

Publications for Loeys-Dietz Syndrome 5

Variations for Loeys-Dietz Syndrome 5

UniProtKB/Swiss-Prot genetic disease variations for Loeys-Dietz Syndrome 5:

75
# Symbol AA change Variation ID SNP ID
1 TGFB3 p.Cys409Tyr VAR_070924 rs398122984

ClinVar genetic disease variations for Loeys-Dietz Syndrome 5:

6 (show all 18)
# Gene Variation Type Significance SNP ID Assembly Location
1 TGFB3 NM_003239.4(TGFB3): c.1226G> A (p.Cys409Tyr) single nucleotide variant Pathogenic rs398122984 GRCh37 Chromosome 14, 76425543: 76425543
2 TGFB3 NM_003239.4(TGFB3): c.1226G> A (p.Cys409Tyr) single nucleotide variant Pathogenic rs398122984 GRCh38 Chromosome 14, 75959200: 75959200
3 TGFB3 NM_003239.4(TGFB3): c.899G> A (p.Arg300Gln) single nucleotide variant Likely pathogenic rs587777617 GRCh37 Chromosome 14, 76429686: 76429686
4 TGFB3 NM_003239.4(TGFB3): c.899G> A (p.Arg300Gln) single nucleotide variant Likely pathogenic rs587777617 GRCh38 Chromosome 14, 75963343: 75963343
5 TGFB3 NM_003239.4(TGFB3): c.754+2T> C single nucleotide variant Pathogenic rs875989816 GRCh37 Chromosome 14, 76431929: 76431929
6 TGFB3 NM_003239.4(TGFB3): c.754+2T> C single nucleotide variant Pathogenic rs875989816 GRCh38 Chromosome 14, 75965586: 75965586
7 TGFB3 NM_003239.4(TGFB3): c.898C> T (p.Arg300Trp) single nucleotide variant Pathogenic rs796051885 GRCh37 Chromosome 14, 76429687: 76429687
8 TGFB3 NM_003239.4(TGFB3): c.898C> T (p.Arg300Trp) single nucleotide variant Pathogenic rs796051885 GRCh38 Chromosome 14, 75963344: 75963344
9 TGFB3 NM_003239.4(TGFB3): c.704delA (p.Asn235Metfs) deletion Pathogenic rs875989817 GRCh37 Chromosome 14, 76431981: 76431981
10 TGFB3 NM_003239.4(TGFB3): c.704delA (p.Asn235Metfs) deletion Pathogenic rs875989817 GRCh38 Chromosome 14, 75965638: 75965638
11 TGFB3 NM_003239.4(TGFB3): c.787G> C (p.Asp263His) single nucleotide variant Uncertain significance rs796051886 GRCh37 Chromosome 14, 76429798: 76429798
12 TGFB3 NM_003239.4(TGFB3): c.787G> C (p.Asp263His) single nucleotide variant Uncertain significance rs796051886 GRCh38 Chromosome 14, 75963455: 75963455
13 TGFB3 NM_003239.4(TGFB3): c.412T> G (p.Ser138Ala) single nucleotide variant Uncertain significance rs201453600 GRCh38 Chromosome 14, 75971659: 75971659
14 TGFB3 NM_003239.4(TGFB3): c.412T> G (p.Ser138Ala) single nucleotide variant Uncertain significance rs201453600 GRCh37 Chromosome 14, 76438002: 76438002
15 TGFB3 NM_003239.4(TGFB3): c.321dup (p.Phe108Ilefs) duplication Pathogenic GRCh38 Chromosome 14, 75980573: 75980573
16 TGFB3 NM_003239.4(TGFB3): c.321dup (p.Phe108Ilefs) duplication Pathogenic GRCh37 Chromosome 14, 76446916: 76446916
17 TGFB3 NM_003239.4(TGFB3): c.927-1G> C single nucleotide variant Likely pathogenic rs767548724 GRCh37 Chromosome 14, 76427420: 76427420
18 TGFB3 NM_003239.4(TGFB3): c.927-1G> C single nucleotide variant Likely pathogenic rs767548724 GRCh38 Chromosome 14, 75961077: 75961077

Expression for Loeys-Dietz Syndrome 5

Search GEO for disease gene expression data for Loeys-Dietz Syndrome 5.

Pathways for Loeys-Dietz Syndrome 5

Pathways related to Loeys-Dietz Syndrome 5 according to KEGG:

37
# Name Kegg Source Accession
1 MAPK signaling pathway hsa04010
2 FoxO signaling pathway hsa04068
3 Cell cycle hsa04110
4 TGF-beta signaling pathway hsa04350
5 Hippo signaling pathway hsa04390

GO Terms for Loeys-Dietz Syndrome 5

Sources for Loeys-Dietz Syndrome 5

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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